Archives

Posts Tagged ‘white blood cells’

It appears that I’m over whatever I had. My nose has stopped running, and my slight cough has resolved as well. I felt a bit under the weather yesterday, but I’m feeling better today—not as good as before this scare, but I’m getting stronger again.

So much of this process is unknown, but a lot is known. One of the things we know is that slightly immature T-cells are responsible for initiating immune responses against viruses. When these T-cells come in contact with other cells that are infected with viruses (or that are otherwise presenting “foreign” chemicals), they do a variety of things that ultimately cause the infected cells to die. But this process takes time, and the infection can spread in the meantime. So, one of the things these immature T-cells do to help with future infection from the same virus is they give rise to more specialized cells. Some of the resulting differentiated T-cells are known as Cytotoxic T-cells (or sometimes CTs, or CD8 cells, where CD refers to a group of proteins on the surface of the cell membrane, deemed Clusters of Differentiation. CTs, or CD8 cells are also sometimes also called T8 lymphocytes, but I’ll just stick to CTs).

CTs are one of many kinds of so-called memory cells; they retain a special chemical affinity (a “memory”) for cells infected with a specific virus, and when the CTs encounter infected cells again, they kill them on the spot—a much faster solution than the slower process that happens the first time infection occurs. This, coupled with other systems, is why once we’ve had a virus, we’re forever immune.

The problem for me is, I don’t really have any T-cells at all. My new immune system is not developed enough to have created any mature T-cells or even any of the slightly immature T-cells needed to initiate the response described above. And that means I don’t yet have any Cytotoxic T-cells from my donor marrow. As CTs are long-lived memory cells, I presumably have circulating in my peripheral blood some of my original, native T-cells that survived the stem cell transplant, but that doesn’t appear to be true. We know this because of the results of my most recent chimerism tests—genetic tests that determine the proportion of peripheral blood cells that are of my genotype versus my donor’s genotype. (Remember that my blood is a chimera right now, like Dictyostelium—part original cells, part donor cells).

Those genetic tests, performed a month ago, show that when considering all of my T-cells, 97% are donor genotype. Those 97% are very immature (too immature to give rise to CTs), and the remaining 3% are what’s left from my former immune system. And while this 3% no doubt includes mature T-cells, and some CTs, they just aren’t very clinically effective for most people (so says my physician). Hammered from the chemotherapy of the transplant? The radiation? Too few to mount a defense? I’m not sure, but they’re impact is apparently thought to be minimal in any event.

But something has changed. I had these symptoms, and now they’re gone. Maybe I beat a virus somehow; maybe it was allergies. I guess I don’t care too much, except from an academic position. But one thing is certain: It couldn’t have been that crystal I shoved up my butt. I only did that an hour ago.

My last post was an honest and authentic expression of my thoughts and feelings about my current state of being. I wasn’t hiding anything. But there is something else going on.

This morning I awoke with a runny nose and some congestion. This could be a minor bacterial infection, which would not likely be a problem to snuff out. But, given that my mucus is clear, bacterial infection seems unlikely. Viral infection is more consistent with that sign. It could be one of a number of common viruses that cause runny nose. For some of these, anti-viral treatments are available. For many, the viruses don’t even have names, but they don’t cause dangerous infections either. I’m hoping for one of these, of course. It could be the flu, and (despite rapidly increasing resistance) that is treatable with osteltamivir. But it could be something much more dangerous: the seemingly innocuous, simple, common cold.

While the common cold causes the mildest of infection in immunocompetent people, in me, it could be a disaster. Permanent scarring of the lungs is one outcome; death is another. As no treatment for the common cold exists (though a number of experimental therapies are soon to help out), recovery relies on one’s immune system entirely. Chicken soup may soothe, but it doesn’t cure.

Viral infections are defeated by lymphocytes. The two main groupings of lymphocytes are T-cells and B-cells. T-cells circulate in our blood, looking for proteins that are not self. When one is found, the T-cell starts dividing, and some of those T-cells seek out B-cells. The T-cells notify B-cells of the presumptive invader, and through one of the most amazing biological processes ever elucidated, germ-specific antibodies are produced. Those antibodies ultimately cause cells infected with viruses to die (among other things).

So T-cells initiate (and later suppress) immune response. B-cells primarily give rise to antibodies. The problem for me is that I don’t have very many of either of these cells. Unlike neutrophils (white blood cells that primarily fight bacterial infection) and platelets, many developmental intermediates come between stem cell and mature lymphocyte, and it can take up to nine months for mature lymphocytes to appear after transplantation. I do have a few lymphocytes from before the transplant, but it’s not clear that they will be of much use.

At this point, I just have to wait. If matters get worse, I’ll get a nose swab tomorrow. That might reveal a treatable virus or an untreatable virus. Maybe I don’t have a virus. I just don’t know right now, but in addition to being energetic and happy, I’m starting to get pretty scared.

I am so energetic, I can barely contain it. Anyone who has spoken to me on the phone lately can attest. For the last two weeks, my energy and strength has been rising every day, and now I feel better than I’ve felt in years. In early 2007, I was in a brief remission, and I felt wonderful, like I’d felt years before—before the fatigue set it, which happened three full years before my diagnosis in 2006. I now feel as good as I did during my remission, which can only be good news.

Reasons for my quick recovery are many: Being able to eat, no more diarrhea, and, most recently, the cessation of a particularly nasty treatment. That treatment, with the drug ganciclovir, is for infection with CMV, cytomegalovirus, thea virus that in healthy people causes mononucleosis‡. I was taking this drug probably because of a hospital error. In order to explain, a brief digression into biology is required. (Regular readers shouldn’t be much surprised.)

CMV is one of the most commonly transmitted viruses on the earth. The probability of contracting CMV rises with every year over one’s lifetime, and virtually everyone has it by middle age. Despite this, I luckily tested negative in my pre-transplant blood tests. Even more luckily, my donor was also negative. This was great news, as CMV can cause blindness, serious lung problems, meningitis, and death in immunosuppressed people—facts that I remember all too well from my AIDS activism days in the late ’80s and early ’90s. My early blood tests found no antibodies for CMV, and a highly sensitive test for CMV’s DNA, called PCR (for polymerase chain reaction), also showed negative initially. However, three weeks into my transplant, a weekly PCR test was positive. This was somewhat odd.

CMV is a herpes virus, and like all herpes viruses (including the virus that causes chickenpox [Herpes zoster]; Epstein-Barr virus; and of course, Herpes simplex I and II), CMV can hide inside cells that it infects, inserting itself into our cellular DNA. When this is the case, a DNA test of blood might well be negative. So if the CMV became active later, a previously negative PCR could become positive. That part wasn’t the odd piece. The odd part was my antibody negativity.

Antibodies are those amazing, disease-specific chemicals that our body produces in response to invasion by viral infections. For every virus that infects us, we have a different antibody (well, almost). But I was antibody negative for CMV, and that was the weird piece. If I had been infected before, and the CMV had become quiescent, and then reactivated three weeks after my transplant, I would’ve been antibody positive the whole time. But despite my suspicions of the apparently discordant blood tests, the positive PCR meant action had to be taken, and fast. Because of the great risk of CMV infection, my physician rightly put me on ganciclovir immediately.

The great thing about ganciclovir is that it is very successful in defeating CMV. I remember when ganciclovir came to market; it was a revolution for people with AIDS. Prior to ganciclovir, having AIDS often meant the loss of sight, or worse. And nothing could be done to stop CMV. Ganciclovir changed all that. But the bad news about ganciclovir is that it suppresses the production of blood cells, especially white blood cells. After I began taking the ganciclovir, all of the components of my blood—my platelets, red blood cells, and white blood cells all crashed. After an unusually fast and strong engraftment of my donor’s stem cells, which resulted in my having normal or near-normal blood counts for the first time in years, I was back to square one, and continuing to take the drug kept me there. And to boot, after this blood cell crash, I contracted that awful C. difficile infection. Administration of ganciclovir has a known association with infections like C. difficile. I had to be treated for the apparent CMV infection, but the treatment made me fragile.

Two weeks ago, my DNA test for CMV was negative, as it had been every time after the first test. I asked my physician why I would not have anti-CMV antibodies if I had CMV (again, antibodies are always produced when we’re exposed to an infection, and we keep them forever). After some discussion, my physician agreed that this was odd, and hypothesized that perhaps I’d acquired the CMV infection from one of my many pre- and post-transplant blood transfusions. But that didn’t explain everything, and I left that meeting unconvinced.

Over the next week I puzzled over all my clinical data. Why was I antibody negative? Maybe it was because my immune system was so shot that it couldn’t produce any antibodies. That is very likely true, but even so, I should still have residual (and easily detectable) antibodies from before the transplant, as they remain in the blood months after they are created. Considering the DNA tests, I wondered how the ganciclovir could have eradicated the infection so quickly; I’d started taking the drug on a Thursday evening, and by the following Tuesday morning all evidence of the viral DNA was gone. Ganciclovir is a good drug, but that good? I asked about this the following week (last week). My physician—who is remarkable in being open to discussion and input—considered my concerns and took a third look at the data, treating them all together. The negative antibody test, the lone positive PCR result, and the rapid PCR negativity that never reversed—they just didn’t add up. After this, my physician concluded that the first CMV test may well have been a false negativepositive (this can happen with PCR, because this DNA test is extremely sensitive, and in labs where these tests are run routinely [like mine], contamination can be a serious problem). As a result, we decided to stop the ganciclovir. My blood cells, in theory, should begin to rise again.

So, yesterday when Greg and I went to the hospital for my weekly appointment, we were a bit disappointed that my blood cells had not rebounded more. My hematocrit (one measure of red blood cells) was a bit higher, my white blood cells had gained 500 cells per squared cm (up from ~1,100), but my platelets were down from 80,000 to 50, 000 (both well below normal)—a mixed result.

But given how amazing I feel, I wasn’t too worried about this. I did ask about the possibility of graft failure—a topic I’ll take up a bit later—but looking at the data on the proportion of “my” blood cells that are truly mine verses from my doner, everything looked excellent.

Stem cell transplant is an unlikely business. Juggling all the variables—the risk of infection, the risk of Graft Versus Host Disease, the many drugs, the side effects of those drugs—managing all these can all be . . . well . . . at times impossible for both the physician and patient. This procedure is truly at the bleeding edge of our knowledge, and much of what goes on, and why certain aspects of the therapy work or don’t, is yet unknown. When in a situation like this, in my experience two factors are indispensable: patient self-advocacy, and physician finesse. Having cut my teeth on AIDS activism, I have no problem telling physicians that this is my body, and we must work together, as co-equal partners, to manage my illness, treatments, and recovery. My current physician agrees, unusually, and we cooperate to achieve our common goal. That cooperation is a big part of why I’m so energetic and healthy today.

That’s what I got today. Except for not knowing if the cancer is really gone . . . and my magnesium levels are not back yet, and my C. difficile sample won’t be finished until tomorrow, and my white blood cells were down slightly. But in general, I’m doing great. And I have to say, I have more energy than I’ve had since my oh-so-short remission in 2007. And the water is clean again.

One of the drugs I’m on for immunosuppression makes me shake constantly. It’s getting annoying. This side effect, coupled with the neuropathy in my hands, makes simple tasks, like lifting a fork, difficult. I wonder if this is a glimpse into how people with Parkinson’s feel? Probably nowhere nearly as bad, but it bites nonetheless.

The drug, tacrolimus, is not used widely for stem cell transplants, but is used generally for kidney transplants. It’s strange that I’m struggling to rebuild my immune system, and I’m taking drugs to slow that process way down. But this is part of the dance—coaxing the new cells to slowly, ever so slowly open their eyes, and think that what they see is self. If they wake up too quickly, they’ll see clearly and attack.

A related immunosuppressive drug that I’m taking, sirolimus, is used probably by even fewer stem cell transplant centers, but the data on this drug are impressive. As an inhibitor of the mammalian Target Of Rapamycin (mTOR; indeed, sirolimus is rapamycin), it blocks a complex cascade by which cells proliferate, and so all is slowed down. The new cells are very sleepy.

I’m very lucky to have these drugs. My current physician is rare in that he does clinical research, and he is actually good at it (this is rare among physicians). These immunosuppressive drugs, coupled with other novel treatments, are the reason my hospital’s success with stem cell transplants is so much higher than the national average. Every day I am grateful that I have the care I have (and my praising physicians is as rare as their conducting good research, so that should tell you how confident I am in my physician).

It is worth noting that both of these chemicals are natural derivatives of bacteria: tacrolimus comes from one species of Streptomyces, sirolimus from another species of the same genus. In fact, most of the chemotherapies I’ve had are naturally occurring biological products. Vincristine—one of the first chemotherapies I ever took, and a potent inhibitor of cell division—comes from the Madagascar periwinkle, once placed in the genus Vinca, where the drug gets its name. Adriamycin, a chemotherapy that damages DNA directly, is also derived from bacteria. And an experimental drug currently showing great promise, Gossypol, is an unaltered, direct extract of the cotton plant, found in the stems, roots and seeds. This drug directly blocks bcl-2, the epicenter of my cancer’s existence, but more on that later.

I could go on and on. Hundreds of our pharmaceuticals come directly from natural sources. The only difference between so-called “natural” medicine and “western” medicine, again, is that the latter is subjected to careful testing, and the former is not.

As I mention in the About page, this blog is not going to be a diary of pain and suffering. Nor will it be a record of hopeful triumph, courage, bravery, and . . . vomit (well, it probably will be about vomit from time to time. I certainly have been doing enough of that). Yes, sometimes I’ll write as though I’m making a diary entry: what happened to me today, or recounting a past event. I do want the blog to relate those experiences. But I’m also just putting down my thoughts about cancer—those shaped by my training as a biologist and as a person who has cancer. But now, a first of the diary-type entries.

Today was a rough day in a string of rough days. Immediately after my transplant, I had a typical litany of fairly minor problems: bacteria in my skin causing folliculitis, fungus in my crotch causing me to want to scratch myself to death, no platelets, no red blood cells, and of course no white blood cells. This is what happens when your bone marrow is destroyed so that another’s can take up root. So, I wasn’t surprised, and it wasn’t that bad. The first week I was pretty pleased with how easy it was.

Then came the fatigue. And I mean fatigue. As is usual, everyone at the hospital told me, “Oh, yeah, that’s very common” after I was blindsided by it. But I shouldn’t have been so blindsided; remaking your entire supply of blood cells is pretty heavy lifting. If I missed a single meal, I thought I would die. I had no spare energy. Not a bit. But once I got used to that, all was well. My new stem cells engrafted very quickly and started making for me a shiny new population of blood cells. My white blood cells came first, as they do, and my platelets shot up to within normal levels shortly thereafter. I was feeling great.

Then about a two weeks ago came the change: Excruciating bowel pain, leg pain, diarrhea, among others. After a spike in fever, I was admitted to the hospital, and after a blizzard of tests, it was discovered that I had Clostridium difficile. I had actually been tested for this bacterium the week before, but the results were negative then.

This germ normally lives in our guts, but with all the antibiotics I’d been eating, the bacteriological ecology of my intestines had been altered, and a new force was on the rise. I’ve been dealing with the trauma of that force since, and the drugs I’m on are working, but slowly. Those drugs also suppress my new blood cells, so many of my cell lines have fallen dangerously low again. I’m still having problems with my blood chemistry, because of the diarrhea; I’m still in a lot of pain (though less); and I still can’t eat much, which means I’m tired most of the time.

My nurse told me today, “Endure, endure!” She sounded like Whitman, and it gave me some strength.